Ammonia monoalkylation

Unfortunately, these reactions don t stop cleanly after a single alkylation has occurred. Because ammonia and primary amines have similar reactivity, the initially formed monoalkylated substance often undergoes further reaction to yield a mixture of products. Even secondary and tertiar) amines undergo further alkylation, although to a lesser extent. For example, treatment of 1-bromooctane with... 

The direct high-pressure animation of ethylene with ammonia to give ethylamine occurs in the presence of acidic zeolite catalysts such as H-elinoptilolite, H-erionite or H-offretite38. Primary amines R1NH2(R1 = Bu, cyclohexyl, PhCH2, Ph or Ar) have been monoalkylated by reaction with di-t-butyl dicarbonate, followed by successive treatment of... 

Benzyl-6-methylcyclohexanone has been prepared by the hydrogenation of 2-benzylidene-6-methylcyclohexanone over a platinum or nickel catalyst, and by the alkylation of the sodium enolate of 2-formyl-6-methylcyclohexanone with benzyl iodide followed by cleavage of the formyl group with aqueous base. The 2,6-isomer was also obtained as a minor product (about 10% of the monoalkylated product) along with the major product, 2-benzyl-2-methylcyclohexanone by successive treatment of 2-methylcyclohexanone with sodium amide and then with benzyl chloride or benzyl bromide. Reaction of the sodium enolate of 2-formyl-6-methylcyclohexanone with potassium amide in liquid ammonia formed the corresponding dianion which was first treated with 1 equiv. of benzyl chloride and then deformylated with aqueous base to form 2-benzyl-2-methylcyclohexanone.i ... 

The other method consists of monoalkylation of ammonia using 2-chloro-l-phenyl-propane [3],... 

Gabriel synthesis, which is most often considered as a classical approach to primary amines, can be generalized as monoalkylation of a suitably protected ammonia derivative with subsequent removal of the phthaloyl group from nitrogen. Despite its wide applicability this procedure suffers, however, from several drawbacks ... 

Primary amines.9,22,62 Direct amination of chloromethyl-trimethylsilane illustrates the diliiculty of stopping the reaction at the monoalkylation level with the formation of up to 30% of the bis(trimethylsilylmethyl) amine even when a large excess of ammonia is employed. The same process has been used to prepare aminomethylsiloxanes where the formation of a small amount of the secondary amine is also observed.63 See also Ref. 24. 

The Sn2 reaction of amines with alkyl halides is complicated by a tendency for overalkylation to form a mixture of monoalkylated and polyalkylated products (Section 19-11). Simple primary amines can be synthesized, however, by adding a halide or tosylate (must be a good SN2 substrate) to a large excess of ammonia. Because there is a large excess of ammonia present, the probability that a molecule of the halide will alkylate ammonia is much larger than the probability that it will over-alkylate the amine product. 

The resulting product is a mixture of dialkyl and monoalkyl phosphate esters. These products also contain small amounts of condensed phosphates and phosphoric acid. Neutralization of the acids with bases like alkali hydroxides, ammonia, or amines produces water-soluble anionic surfactants and emulsifiers. 

For the preparation of secondary and tertiary amines by monoalkylation of, respectively, primary and secondary amines by alkali halides there are as few satisfactory prescriptions in the literature as there are for the reaction with ammonia. The main difficulties have been mentioned above. 

Monoalkylation of primary amines proceeds more smoothly than dialkylation of ammonia. Only formaldehyde readily reacts further to give the tertiary amines. Other aliphatic aldehydes afford good yields of secondary amine if aldol condensation is avoided by adding the aldehyde gradually to the reaction mixture. 

The amide back reaction during alkylation can be minimized or even eliminated by inverse-quenching procedures. When the metal-ammonia solutions of anthracene or naphthalene are added to an excess of alkyl halide, dramatic changes in the ratio of mono- to dialkylated products result (see Table I). The predominance of monoalkylation with inverse quenching certainly supports the presence of monoanions. Perhaps even the minor amounts of dialkylated products formed by inverse quenching are still being formed by a back reaction. 

Monoalkylated TosMIC 222 reacts with 209 to furnish, after lithium—ammonia deprotection, (4 5,55)-5-pentyl-4-hydroxymethyl-2,2-dimethyl-l,3-dioxolane (223). This is smoothly converted in four steps to (4iS, 55)-5-hydroxy-4-decanolide (L-factor) (224), the proposed autoregulator isolated from mutant strains of Streptomyces grieseus [79] (Scheme 52). 

Use of nonionic surfactant, Triton X, with a cinchonidinium based PT catalyst to accelerate the alkylation step Aldol condensation in the presence of NaOH and a PT catalyst N-alkylation of carbazones, phenothiazines, acridanone, and indoles using alkyl ahalides and aqueous NaOH/solid K2CO3 Facile and selective monoalkylation of the indole nitrogen using PTC, instead of using K azide in liquid ammonia at —40°C 0-alkylation using r-butylbromoacetate... 

Metaphosphates undergo various reactions with ammonia to produce amido derivatives, ammonium salts and cycloimidophosphates (Chapter 7). Alcohols will react under alkaline conditions to give monoalkyl straight-chain esters. 

Copper(I) iodide reacts with monoalkyl and arylethynes in aqueous ammonia giving insoluble yellow, red or brown derivatives [Cu—C=CR] . These reactions resemble those of mercury(II) (p. 61). These acetylides couple with aryl iodides... 

If the quaternary ammonium salt is the desired product, then an excess of the alkyl halide is used, and ammonia is said to undergo exhaustive alkylation. However, monoalkylation is difficult to achieve because each successive alkylation renders the nitrogen atom more nucleophilic. If the primary amine is the desired product, then the process is generally not efficient because when 1 mol of ammonia is treated with 1 mol of the alkyl halide, a mixture of products is obtained. For this reason, the alkylation of ammonia is only useful when the starting alkyl halide is inexpensive and the desired product can be easily separated or when exhaustive alkylation is performed to yield the quaternary ammonium salt. 

Monoalkylation of ammonia is difficult to achieve because the resulting primary amine is even more nucleophilic than ammonia. 

These alkylation reactions of amines are so efficient that it is difficult to stop at monoalkylation. However, Theodore Cohen (b. 1929) and his co-workers at the University of Pittsburgh worked out a method that uses ammonia in excess under pressure to generate primary amines efficiently. The vast excess of ammonia means that it is difficult for the initial alkylated product, methylamine, to compete with ammonia for a molecule of methyl iodide (Fig. 7.112). 

The preparation of dialkylamines from ammonia or primary amines can be realised where steric factors militate against tertiary amine formation. Thus monoalkylation of f-butylamine with some alkyl halides and epoxides has been accomplished (reaction 41) . 

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